PAN-OMICs TECHNOLOGY CORE SUMMARY The objective of the Pan-OMICs Technology Core (PTC) is to provide state-of-the-art, innovative -OMICs technologies for the targeted and global characterization of Project samples in a quantitative, reproducible, and efficient manner. The PTC brings together cutting-edge tools and the expertise of leading systems biologists in three critical areas: (1) Genomics led by Dr. Chris Benner at the University of California, San Diego; (2) Proteomics led by Dr. Nevan Krogan at the J. David Gladstone Institutes; and (3) Metabolomics led by Drs. Ed Dennis and Oswald Quehenberger at the University of California, San Diego (lipidomics) as well as by Dr. Leah Shriver at the University of Akron (polar metabolites). The PTC will be responsible for receiving, processing, and analyzing both in vivo samples from infected patients and mice (Project 1) as well as ex vivo infected samples in culture (Project 2). These data will be integrated by the Modeling Core to identify key drivers of influenza virus infection, biomarkers of disease severity, and potential nodes for therapeutic intervention. Upon perturbation of these critical drivers by each respective Project, the PTC will provide these same services in a comparative manner to determine specific, functional consequences of such perturbations for the determination of molecular mechanism. This iterative cycle from systems-to-mechanism is driven by the Pan-OMICs Technology Core integrating multiple labs and Projects to optimally leverage best-in-class -OMICs approaches to map the molecular pathways surrounding influenza virus infection and disease. The PTC has a uniquely challenging and rewarding directive in the generation and integration of coordinated systems data spanning chromatin modifications and architecture, gene expression, protein abundance, post- translational modifications, protein-protein interactions, lipid profiling, and polar metabolite identification. In the previous iteration of our Fluomics consortium, Drs. Benner, Krogan, Dennis, Quehenberger, and Shriver worked extensively together to tackle these challenges and derive standardized protocols for sample generation, processing, and analysis between different cores and institutes. Formalizing this relationship as a single core under the leadership of Dr. Nevan Krogan, an internationally recognized expert in the design and application of systems biology approaches to interrogate host-pathogen interactions, the PTC is ideally positioned to both effectively and efficiently implement these previously developed pipelines for the accomplishment of our Aims.